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Amino acid sequence environment modulates the disruption by osteogenesis imperfecta glycine substitutions in collagen-like peptides.
Biochemistry. 1997 Jun 10; 36(23):6930-5.B

Abstract

Ostoegenesis imperfecta (OI) or "brittle bone" disease is associated with mutations in the genes for type I collagen chains and produces variable phenotypes, ranging from lethal cases at birth to mild cases with increased bone fractures. The most common OI mutations are single base substitutions leading to replacement of Gly by another residue, breaking the typical (Gly-X-Y)n repeating sequence pattern of the collagen triple-helix. Triple-helical peptides were designed to focus on residues 892-921 of the alpha1 chain of type I collagen, where two OI Gly-->Ser mutations are found in close proximity, a mild mutation at site 901 and a lethal mutation at site 913. Peptides were designed to include amino acid sequences around these mutation sites, and were synthesized with the normal sequence or with the Gly-->Ser mutated sequence. The peptide including the normal sequence residues 892-909 with four Gly-Pro-Hyp triplets at the C-terminus formed a stable triple-helix, and introduction of a Ser residue for Gly at the 901 mutation site led to a 50% loss of triple-helix content and a decrease in thermal stability, with little effect on folding. A peptide including residues 904-921 again formed a stable triple-helix, but the introduction of the Gly-->Ser substitution at site 913 led to a much greater decrease in thermal stability. These studies demonstrate the impact of local sequences flanking the Gly substitution on structural consequences and support the concept of variability and regional effects along the collagen molecule.

Authors+Show Affiliations

Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9188687

Citation

Yang, W, et al. "Amino Acid Sequence Environment Modulates the Disruption By Osteogenesis Imperfecta Glycine Substitutions in Collagen-like Peptides." Biochemistry, vol. 36, no. 23, 1997, pp. 6930-5.
Yang W, Battineni ML, Brodsky B. Amino acid sequence environment modulates the disruption by osteogenesis imperfecta glycine substitutions in collagen-like peptides. Biochemistry. 1997;36(23):6930-5.
Yang, W., Battineni, M. L., & Brodsky, B. (1997). Amino acid sequence environment modulates the disruption by osteogenesis imperfecta glycine substitutions in collagen-like peptides. Biochemistry, 36(23), 6930-5.
Yang W, Battineni ML, Brodsky B. Amino Acid Sequence Environment Modulates the Disruption By Osteogenesis Imperfecta Glycine Substitutions in Collagen-like Peptides. Biochemistry. 1997 Jun 10;36(23):6930-5. PubMed PMID: 9188687.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amino acid sequence environment modulates the disruption by osteogenesis imperfecta glycine substitutions in collagen-like peptides. AU - Yang,W, AU - Battineni,M L, AU - Brodsky,B, PY - 1997/6/10/pubmed PY - 1997/6/10/medline PY - 1997/6/10/entrez SP - 6930 EP - 5 JF - Biochemistry JO - Biochemistry VL - 36 IS - 23 N2 - Ostoegenesis imperfecta (OI) or "brittle bone" disease is associated with mutations in the genes for type I collagen chains and produces variable phenotypes, ranging from lethal cases at birth to mild cases with increased bone fractures. The most common OI mutations are single base substitutions leading to replacement of Gly by another residue, breaking the typical (Gly-X-Y)n repeating sequence pattern of the collagen triple-helix. Triple-helical peptides were designed to focus on residues 892-921 of the alpha1 chain of type I collagen, where two OI Gly-->Ser mutations are found in close proximity, a mild mutation at site 901 and a lethal mutation at site 913. Peptides were designed to include amino acid sequences around these mutation sites, and were synthesized with the normal sequence or with the Gly-->Ser mutated sequence. The peptide including the normal sequence residues 892-909 with four Gly-Pro-Hyp triplets at the C-terminus formed a stable triple-helix, and introduction of a Ser residue for Gly at the 901 mutation site led to a 50% loss of triple-helix content and a decrease in thermal stability, with little effect on folding. A peptide including residues 904-921 again formed a stable triple-helix, but the introduction of the Gly-->Ser substitution at site 913 led to a much greater decrease in thermal stability. These studies demonstrate the impact of local sequences flanking the Gly substitution on structural consequences and support the concept of variability and regional effects along the collagen molecule. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/9188687/Amino_acid_sequence_environment_modulates_the_disruption_by_osteogenesis_imperfecta_glycine_substitutions_in_collagen_like_peptides_ L2 - https://doi.org/10.1021/bi970051h DB - PRIME DP - Unbound Medicine ER -